ABSTRACT After almost two decades of research and quality improvement, hospitalized children in the US are safer from healthcare-related harm. The vast-majority of healthcare, however, is provided in the clinic and at home, and few studies in this context have demonstrated how to improve safety. Children are especially vulnerable to preventable harm caused by healthcare for many reasons, including weight-based medication dosing, handoffs between caregivers, and their limited ability to communicate evolving symptoms. At home, two in five children with chronic disease have a medication error. Of these, 3.6% are injured due to these errors?the same rate as hospitalized children. Among the 165,000 children with type 1 diabetes (T1D) nationally, 20% have poor glycemic control. The leading cause of death before age 30 among individuals with T1D is acute complications (e.g., severe hypoglycemia, diabetic ketoacidosis). One in 68 children have autism spectrum disorder (ASD). Of these children, 40% take antipsychotic medications, and most are not screened for complications. Management of chronic conditions with families is complex and offers a myriad of opportunities for system failures to occur that can lead to patient harm. We have identified 3 key opportunities to reduce the 2 most egregious harms in this setting?medication errors and treatment delays?in 2 different conditions. The Ambulatory Pediatric Patient Safety Learning Lab aims to: 1. Redesign processes for adjustment of medication dosing based on clinical information gathered by the patient/family to prevent medication errors. (This will be studied in type 1 diabetes) 2. Create processes for patient/family medication monitoring and communication with clinic to prevent adverse drug events. (This will be studied in children with Autism spectrum disorder on antipsychotics) 3. Design a workflow to plan for, detect and prompt management of serious illness among children with chronic conditions at home (This will be studied in both populations) This learning lab integrates design and systems engineering?in collaboration with Mad*Pow, and University of Wisconsin Systems Engineering Initiative for Patient Safety?with Cincinnati Children?s expertise in patient- centered research and implementation. The overarching goal is to redesign systems of care and coordination between the clinic and home to eliminate harm due to healthcare in these settings. Problem analysis will include ethnography in the home and clinic, interviews, FMEAs, and digital diaries. We will implement all interventions together in the simulated environment and evaluate using a randomized factorial trial. Finally, we will implement in our clinical system with qualitative and quantitative evaluation. The intent is to develop a scalable model which leverages health systems and patient/family strengths to ensure safe healthcare among all children. Upon completion of this proposal, our team is perfectly poised to scale this nationally through the Solutions for Patient Safety (SPS) Network and improve pediatric ambulatory safety across the US.